Ln3TCAS2-polyethyleneimine supramolecular nanogels: a platform for neutron capture therapy and complementary magnetic resonance imaging (Ln = lanthanide, TCAS = thiacalix[4]arene-p-tetrasulfonate).

Supramolecular nanogels with high drug-loading capacity were prepared via electrostatic crosslinking of cationic polyethyleneimine (PEI) with hepta-anionic lanthanide complexes, Ln3TCAS2 (Ln = Tb, Gd; TCAS = thiacalix[4]arene-p-tetrasulfonate), which act as both structural crosslinkers and theranostic agents. The optimized nanogels exhibited a hydrodynamic diameter of 163 nm (suitable for endocytotic uptake), a highly positive ζ-potential (+50 mV), and an exceptionally high loading capacity of 45%. Notably, the nanogels demonstrated robust colloidal stability with a negligible complex leakage rate (0.034%) under physiological conditions. For magnetic resonance imaging (MRI), the Gd3TCAS2-PEI nanogels showed an enhanced longitudinal relaxivity (r1 = 8.8 mM-1 s-1 at 0.47 T, 37 °C) compared to the free complex, attributed to prototropic exchange within the PEI matrix. In vitro assays using MCF-7 cells revealed highly efficient cellular uptake (3.63%) via endocytosis, resulting in substantial lysosomal accumulation. This delivered a therapeutically optimal intracellular 157Gd concentration of 84.7 ppm. Consequently, upon thermal neutron irradiation, the nanogel-treated cells exhibited significant neutron capture therapy (NCT) efficacy compared to controls (p < 0.05). Given their highly cationic nature, these nanogels are exceptionally well-suited to bypass systemic toxicity via direct intratumoral injection. These results establish the Ln3TCAS2-PEI nanogel as a highly stable, versatile platform for localized NCT and complementary MR imaging.